This invention relates to the technical sector of systems for the generation of aerosols and sprays for medical purposes.
Aerosols are defined as a suspension of particles in a gas. These particles can range in size from a few nanometers to several tens of micrometers. The purpose of systems for the generation of medical aerosols is to transform medications, a liquid or a powder, into aerosol form to be administered into the respiratory tracts.
The advantage of the aerosol method compared to other methods of administration is the targeting of the organ to be treated by deposition of the medication. Existing nebulizers enable large quantities of medication to be administered into the respiratory tracts. Pulmonary nebulizers target the lungs, nasal nebulizers or sprays target the nasal fossae and the rhinopharynx. As regards nasal nebulizers or sprays, it is theoretically possible to deposit aerosol solely in the nasal fossae, site of the first passage of the aerosol into the airways. A first solution is to use an aerosol with large-sized particles. The problem with an aerosol with a large particle size is that it will not deposit itself in a peripheral and homogenous way in the different compartments of the ENT environment (e.g.: sinus, target site for treating sinusitis) (Suman et al, Pharm Res. 1999, 6:1648-52). The other solution consists in using an aerosol with small-sized particles to try and ensure a “peripheral” deposition in the ENT environment. Moreover, this fine aerosol is capable of depositing itself in the lungs. On the other hand, bearing in mind the anatomy of the nostrils and the rhinopharynx, aerosols penetrating into the nostril will be filtered by the nasal hairs and undergo high acceleration due to the small diameter of the nostrils and the nasal valve (C Croce et al, Ann Biomed Eng. 2006, 34:997-1007). The particles thus conveyed beyond the first centimeters of the nasal fossae will be of a small size incompatible with a deposition by impaction or sedimentation in the rhinopharynx or the sinuses. According to a study conducted with a model head inhaling a 5 μm MMAD aerosol, 82% of the aerosol is deposited in the nose, the nasal valve and the first few centimeters of the nasal fossae, 0.2% in the sinuses, 1% in the rest of the nasal fossae and 26.8% in the lungs (Vecellio, 2002, doctoral thesis). Thus, according to this study by scintigraphic imagery in a plastinated head, only 5% of the aerosol passing through the nasal valve is deposited there.
In the present text, the upper nasal airways can be described as the succession of the following anatomical regions (FIG. 1): the nostrils (2), the nasal valve (5), the nasal fossae (6) and the rhinopharynx (7). The nasal fossae represent the largest anatomical volume and include the ethmoid region, the conchae and the access to the sinus.
The Atomisor NL11 (FR2835435) pneumatic nebulizer poses this problem of targeting the nasal fossae (FIG. 1). In its principle of use, the Atomisor N11 pneumatic nebulizer (1) fitted with its nosepiece (FR2638361) is connected to both nostrils (2), right and left, and generates a 5 μm aerosol in the patient's ENT environment (3) during the inspiratory phase (FIG. 1). During the inspiratory phase (FIG. 1), the aerosol produced by the nebulizer (1) is then directed straight from the ENT environment (3) to the patient's lungs (4). The aerosol produced is then accelerated into the first few centimeters of the nasal fossae and even beyond to the nasal valve (5), which explains its heavy impaction in the first few centimeters of the nostrils. Moreover, the hairs, the first natural element of protection of the respiratory tracts by filtration, intercept the largest particles. The smallest particles having passed through the nasal valve reach the nasal fossae (6), which have a less favourable anatomy for the deposition of particles by impaction than that of the nostrils (slower air speeds than in the nostrils).
Nasal sprays (48) use a nosepiece of sufficient length to ensure the passage of a device through the hairs (FIG. 2). This type of device produces large-sized particles (20 μm to 150 μm) with high speeds of the initial particles ensuring their deposition by impaction. The angle of the spray is therefore an important parameter for ensuring homogeneity of deposition in the rhinopharynx. As described in the literature (Kimbell et al, 2007, J Aerosol Med, 20:59-74), this type of device of administration by spray has limits in its variability of use. In fact, the position and angle of orientation of the device's nosepiece affect the deposition of particles and so the effectiveness of treatment. Moreover, considering the size of the particles and the speed of injection of the particles, it would appear that the particles only just reach the middle nasal fossae (Senocak et al, 2005, Otolaryngology Head and Neck Surgery, 133:944-948) and do not reach the posterior nasal fossae at all (Cheng et al, 2001, J Aerosol Med, 14:267-280) (Guo et al, 2005, Pharm R, 22:1871-1878).
In order to resolve this problem of targeting fine aerosol into the ENT environment, different systems available on the market propose more or less effective solutions.
The PARI Sinus nebulizer implements Patents US2006/0162722 A1 and US2007/0181133 A1. It administers fine aerosol through one nostril, when the patient closes the soft palate, to limit deposition in the lungs and increase deposition in the ENT environment. The aerosol penetrates into one nostril and exits through the other nostril provided with a second nosepiece having a narrow section to increase nasal pressure and promote the penetration of aerosol into the sinuses. This method of administration of the aerosol requires the active participation of the patient. The patient must not inspire or expire during administration of the aerosol and must simultaneously raise his soft palate. As this system demands a very active participation of the patient it can be ineffective if the patient fails correctly to follow the instructions for raising his soft palate. This requires patients to be taught and trained, which is not always achievable due to age constraints. This system does not overcome the heavy deposition in the first few centimeters of the nostrils.
The Optinose system, covered by Patents WO 03/000310 A2, EP1410820A2, US 2006/0107957 A1, US2005/0235992 A1 and US 2006/0096589 A1, also uses the system of penetration of the aerosol into one of the two nostrils and its escape through the other nostril. It also uses an automatic triggering of aerosol generation during the patient's oral expiration phase. Under these conditions, during the inspiration phase, the patient can inspire through the nostril and inhale air containing no aerosol. During the oral expiration phase, the soft palate is raised, and the aerosol produced penetrates into one of the two nostrils. The aerosol is then conveyed from the first nostril to the second nostril and the lungs are protected from any penetration of the aerosol by the seal of the soft palate. The high performance of this system for limiting lung deposition has been proved on healthy patients but the aerosol does not penetrate though a mouthpiece but always through a nosepiece. (Djupesland et al, Bi-directional nasal delivery of aerosols can prevent lung deposition. J Aerosol Med. 2004 Fall; 17(3):249-59). Patent WO2007093784 of the same company also describes a system for aerosol generation only during the nasal expiration phase. The drawback of this system is that the aerosol penetrates through one nostril and not through the mouth, thus the system does not resolve the problem of heavy deposition of aerosol in the first few centimeters of the nostrils.
According to the prior art, it must be acknowledged that the administration of aerosol for the rhinopharynx, nasal cavities or paranasal sinuses is always achieved by means of a nosepiece inserted into the nostrils. This method of administration through the nose is the logical consequence of studies proving the advantage of using a mouthpiece to promote lung deposition. In fact, using a face mask on the patient not only enables inhalation of the aerosol through the mouth but also through the nose, thus limiting lung deposition and promoting rhinopharyngeal deposition. The use of a mouthpiece is therefore recommended for the administration of aerosol for the lungs (Dautzenberg B, Becquemin M H, Chaumuzeau J P, Diot P. 2007. Good practices of aerosol therapy by nebulization. Rev Mal Respir. 24:751-757) and a mouthpiece is recommended for the administration of aerosol for the rhinopharynx. To summarise, the administration of aerosol for the lungs is achieved through the patient's mouth or nose and the administration of aerosol for the nasal cavities is achieved through the patient's nose (Table 1).
TABLE 1Aerosol generators of the prior art and their means of deliverydepending on the respiratory organ to be treated.Aerosol for theAerosolrhinopharynx, nasalpenetrationcavities or paranasalorganAerosol for the lungssinusesMouthMouthpiece (prior art)Mouthpiece (Invention)NoseFace mask (prior art)Nosepiece (prior art)
Also known, through Patent WO 2004/103447, is a device provided with a mouthpiece and an administration tube penetrating deep into the oral cavity in order to ensure deposition of the substance by spraying onto the mucosa or the oral cavity, thus with a targeted projection having an effect limited to a given place.
Also known, through Patent WO 98/533869, is a method for introducing a substance into the nose of a person by using a tubular device in the form of a straw inserted at its first opening into the patient's mouth and at its second opening into the patient's nostril. The patient expires through the mouth into the tubular device so as to transfer the substance into the nostril. During the oral expiration phase the soft palate is raised, sealing the communication between the oral cavity and the nasal cavity. The substance can penetrate into the nasal cavity without the risk of deposition in the patient's oral cavity or lungs. This method is physically impossible in the opposite direction.
These documents therefore have very limited applications and effects.
The Applicant's approach has therefore been to reconsider the problem of this targeting of the ENT environment with an aerosol.
Faced with this situation, the Applicant therefore focused on a different design of this type of equipment.